Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats
Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats
复制标题
低分子量岩藻依聚糖保护糖尿病 Goto-Kakizaki 大鼠的内皮功能并改善基础高血压
DOI：
10.1038/labinvest.2014.12
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发表时间：
2014-04-01
影响因子：
5
通讯作者：
Luo, Dali
中科院分区：
文献类型：
--
作者：
Cui, Wentong;Zheng, Yuanyuan;Luo, Dali
以内皮型一氧化氮合酶（eNOS）和一氧化氮（NO）生物利用度受损为特征的内皮功能障碍与糖尿病心血管发病机制有关。在这项研究中，低分子量岩藻依聚糖（LMWF），它具有多种生物活性，包括抗炎和抗氧化特性，研究其对Goto-Kakizaki 2型糖尿病大鼠内皮功能障碍的保护作用。LMWF（50、100或200 mg/kg/天）或普罗布考（100 mg/kg/天）给糖尿病大鼠12周。基础血压，乙酰胆碱或流量介导的肠系膜和爪动脉，内皮依赖性的主动脉扩张，eNOS磷酸化和NO的生产进行了测量，使用激光多普勒血流仪，力肌描记仪，苏木精和伊红染色，蛋白质印迹分析，和NO测定。我们发现，LMWF稳健地改善糖尿病大鼠的基础高血压和主动脉、肠系膜动脉和足动脉内皮依赖性舒张功能受损。此外，在eNOS磷酸化Ser 1177，eNOS表达，和NO的生产，因为糖尿病的减少部分逆转LMWF治疗。然而，普罗布考，一种具有抗氧化特性的调脂药物，只显示出轻微的影响。此外，LMWF诱导，以剂量依赖性的方式，内皮依赖性血管舒张和eNOS磷酸化Ser 1177在正常主动脉，也促进Ser 1177磷酸化和NO合成在原代培养的血管内皮细胞。因此，这些数据首次表明，岩藻依聚糖保护血管内皮功能，并降低基础血压在2型糖尿病大鼠通过，至少部分地，保护eNOS功能。因此，褐藻糖胶是一个潜在的候选药物，保护内皮细胞在糖尿病心血管并发症。
Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine- or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications.